Pulmonary arterial hypertension (PAH) is a progressive and complex pulmonary vascular disease with poor prognosis. The aim of this study was to provide a new understanding of the pathogenesis of disease and potential treatment targets for patients with PAH based on multiple-microarray analysis.Two microarray datasets (GSE53408 and GSE113439) downloaded from the Gene Expression Omnibus (GEO) database were analysed. All the raw data were processed by R, and differentially expressed genes (DEGs) were screened out by the “limma” package. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed and visualized by R and Cytoscape software. Protein-protein interactions (PPI) of DEGs were analysed based on the NetworkAnalyst online tool. A total of 442 upregulated DEGs and 84 downregulated DEGs were identified. GO enrichment analysis showed that these DEGs were mainly enriched in mitotic nuclear division, organelle fission, chromosome segregation, nuclear division, and sister chromatid segregation. Significant KEGG pathway enrichment included ribosome biogenesis in eukaryotes, RNA transport, proteoglycans in cancer, dilated cardiomyopathy, rheumatoid arthritis, vascular smooth muscle contraction, focal adhesion, regulation of the actin cytoskeleton, and hypertrophic cardiomyopathy. The PPI network identified 10 hub genes including HSP90AA1, CDC5L, MDM2, LRRK2, CFTR, IQGAP1, CAND1, TOP2A, DDX21, and HIF1A. We elucidated potential biomarkers and therapeutic targets for PAH by bioinformatic analysis, which provides a theoretical basis for future study.

Background: Proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab reduce ischemic events; however, the cost-effectiveness remains uncertain. This study sought to evaluate its economic value in patients with myocardial infarction (MI) from the Chinese healthcare perspective.Methods: A state-transition Markov model was developed to determine the cost-effectiveness of alirocumab for preventing recurrent MI, ischemic stroke and death. Preventative effect of the therapy was gathered from ODYSSEY OUTCOMES trial and absolute reduction of low-density lipoprotein cholesterol (LDL-C) in ODYSSEY EAST trial, respectively. The primary outcome was the incremental cost-effectiveness ratio (ICER), defined as incremental cost per quality-adjusted life-year (QALY) gained.Results: Compared with statin monotherapy, the ICER of alirocumab therapy at its present discounted price [34,355 Chinese yuan (CNY) annually, 33% rebate] based on clinical follow-up efficacy was 1,613,997 CNY per QALY gained. A willingness-to-pay threshold of 212,676 CNY per QALY would be achieved when the annual cost of alirocumab was reduced by 88% from the full official price to 6071 CNY. The therapeutic effect evaluation estimated by the magnitude of LDL-C reduction was superior to the results of clinical follow-up, but this medication was still far from cost-effective. Multiple vulnerable subgroup analyses demonstrated that the ICER for patients with polyvascular disease in 3 vascular beds was 111,750 CNY per QALY gained.Conclusion: Alirocumab is not cost-effective in general MI population based on current discounted price. High long-term costs of alirocumab may be offset by health benefit in patients with polyvascular disease (3 beds).